tbuckley/cabot-search huggingface dataset:
Tyrosinase‐activated Nanocomposites for Double‐Modals Imaging Guided Photodynamic and Photothermal Synergistic Therapy
Authors: Shuo Li, Guoyang Zhang, Yanghan Peng, Peiyu Chen, Jiguang Li, Xuefei Wang, Zhuo Wang
Journal: Advanced Healthcare Materials (2023)

Tyrosinase (TYR) is an important biomarker of melanoma. The exploration of fluorescent pr-obes-based composites is beneficial to build an integrative platform for the diagnosis and treatment of melanoma. Herein, a multifunctional nanocomposite IOBOH@BSA activated by TYR is developed for selective imaging and ablation of melanoma. The chemical structure of IOBOH enables the fluorescence (FL) imaging activated by TYR, photoacoustic (PA) imaging, and photodynamic-photothermal activity by regulating the balance between radiative decay and non-radiative decay. IOBOH combined with bovine serum albumin (IOBOH@BSA) presents the response to TYR and realizes FL imaging with mitochondria-targeting in melanoma. Moreover, IOBOH@BSA shows excellent photothermal ability and is applied for PA imaging. After IOBOH@BSA is activated by TYR, the singlet oxygen generation increases obviously. IOBOH@BSA can realize TYR-activated imaging and photodynamic-photothermal therapy of melanoma. The development of TYR-activated multifunctional nanocomposites promotes the precise imaging and improves the therapeutic effect of melanoma.
The alternative approach: genomic classifiers for prognostication in interstitial lung disease
Authors: Gillian C. Goobie, Sabina A. Guler
Journal: European Respiratory Journal (2023)

Interstitial lung disease (ILD) reflects a large group of entities characterised by pulmonary parenchymal inflammation and fibrosis, with many patients suffering from functional limitation, progressive symptoms and accelerated mortality [1]. Idiopathic pulmonary fibrosis (IPF), which is characterised by a usual interstitial pneumonia (UIP) pattern on imaging and histology, is the most common and deadly form of ILD [2, 3]. Prognosis and treatment approaches differ between ILD subtypes, making an accurate diagnosis crucial; however, this can be challenging due to overlapping clinical and morphological presentations of some ILDs. The potential of genomic classifiers for ILD prognostication has not been exhausted yet <http://bit.ly/3ZMMdjx>
Eganelisib, a First-in-Class PI3Kγ Inhibitor, in Patients with Advanced Solid Tumors: Results of the Phase 1/1b MARIO-1 Trial
Authors: David S. Hong, Michael Postow, Bartosz Chmielowski, Ryan Sullivan, Amita Patnaik, Ezra E.W. Cohen, Geoffrey Shapiro, Conor Steuer, Martin Gutierrez, Heather Yeckes-Rodin, Robert Ilaria, Brenda O'Connell, Joanna Peng, Guangbin Peng, Nora Zizlsperger, Anthony Tolcher, Jedd D. Wolchok
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Eganelisib (IPI-549) is a first-in-class, orally administered, highly selective PI3Kγ inhibitor with antitumor activity alone and in combination with programmed cell death protein 1/ligand 1 (PD-1/PD-L1) inhibitors in preclinical studies. This phase 1/1b first-in-human, MAcrophage Reprogramming in Immuno-Oncology-1 (NCT02637531) study evaluated the safety and tolerability of once-daily eganelisib as monotherapy and in combination with nivolumab in patients with solid tumors. Patients and Methods: Dose-escalation cohorts received eganelisib 10–60 mg as monotherapy (n = 39) and 20–40 mg when combined with nivolumab (n = 180). Primary endpoints included incidence of dose-limiting toxicities (DLT) and adverse events (AE). Results: The most common treatment-related grade ≥3 toxicities with monotherapy were increased alanine aminotransferase (ALT; 18%), aspartate aminotransferase (AST; 18%), and alkaline phosphatase (5%). No DLTs occurred in the first 28 days; however, toxicities meeting DLT criteria (mostly grade 3 reversible hepatic enzyme elevations) occurred with eganelisib 60 mg in later treatment cycles. In combination, the most common treatment-related grade ≥3 toxicities were increased AST (13%) and increased ALT and rash (10%). Treatment-related serious AEs occurred in 5% of monotherapy patients (grade 4 bilirubin and hepatic enzyme increases in one patient each) and 13% in combination (pyrexia, rash, cytokine release syndrome, and infusion-related reaction in ≥2 patients each). Antitumor activity was observed in combination, including patients who had progressed on PD-1/PD-L1 inhibitors. Conclusions: On the basis of the observed safety profile, eganelisib doses of 30 and 40 mg once daily in combination with PD-1/PD-L1 inhibitors were chosen for phase 2 study.
Corrigendum to: NCOG-45. Differential and dose-dependent effects of cranial irradiation on brain structures and neuropsychological outcomes in children with posterior fossa brain tumors treated with different modalities
Authors: Sofia Dhanani, Sharon O'neil, Scarlet Cho, Brandon Shin, Marvin Nelson, Kenneth Wong, Arthur Olch, Jeffrey Tanedo, Oliver Biele
Journal: Neuro-Oncology (2023)
SALVO: Single-Arm Trial of Ipilimumab and Nivolumab as Adjuvant Therapy for Resected Mucosal Melanoma
Authors: Lisa A. Kottschade, Gregory Russell Pond, Anthony J. Olszanski, Yousef Zakharia, Evidio Domingo-Musibay, Ralph J. Hauke, Brendan D. Curti, Sarah Schober, Mohammed M. Milhem, Matthew Stephen Block, Tina Hieken, Robert R. McWilliams
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Mucosal melanoma is a rare, aggressive form of melanoma with extremely high recurrence rates despite definitive surgical resection with curative intent. Currently there is no consensus on adjuvant therapy. Data on checkpoint inhibitors for adjuvant therapy are lacking. Patients and Methods: We performed a single-arm, multicenter clinical trial using “flip dose” ipilimumab (1 mg/kg q3w × 4 cycles), and nivolumab (3 mg/kg q3w × 4 cycles), then nivolumab 480 mg q4w × 11 cycles to complete a year of adjuvant therapy. Participants must have had R0/R1 resection ≤90 days before registration, no prior systemic therapy (adjuvant radiotherapy allowed), ECOG 0/1, and no uncontrolled autoimmune disease or other invasive cancer. Patients were recruited through the Midwest Melanoma Partnership/Hoosier Oncology Network. Results: From September 2017 to August 2021, 35 patients were enrolled. Of these, 29 (83%) had R0 resections, and 7 (20%) received adjuvant radiotherapy. Median age was 67 years, 21 (60.0%) female. Recurrence-free survival (RFS) rates at 1 and 2 years were 50% [95% confidence interval (CI), 31%–66%] and 37% (95% CI, 19%–55%), respectively. Overall survival rates at 1 and 2 years were 87% (95% CI, 68%–95%) and 68% (95% CI, 46%–83%), respectively. Median RFS was 10.3 months (95% CI, 5.7–25.8). Most common grade 3 toxicities were diarrhea (14%), hypertension (14%), and hyponatremia (11%), with no grade 4/5 toxicities. Conclusions: Flip-dose ipilimumab and nivolumab after resection of mucosal melanoma is associated with outcomes improved over that of surgical resection alone. Long-term follow-up, subgroup analyses and correlative studies are ongoing.
Panta rhei (Πάντα ῥεῖ), or everything flows with long COVID
Authors: Joan B. Soriano, Jessica González, Antoni Torres
Journal: European Respiratory Journal (2023)

Heraclitus, the Greek, pre-Socratic philosopher (figure 1), believed the world was ultimately made of fire, a metaphor for change. He wrote five centuries BC: panta rhei (Πάντα ῥεῖ, "everything flows"), exemplifying it with his quote: "No man ever steps in the same river twice." No long COVID patient ever steps in the same river twice, as their condition changes continuously due to its natural history, or because of treatment http://bit.ly/3QMFhyK
The neuroscience of music – towards ecological validity
Authors: Mari Tervaniemi
Journal: Trends in Neurosciences (2023)

Studies in the neuroscience of music gained momentum in the 1990s as an integrated part of the well-controlled experimental research tradition. However, during the past two decades, these studies have moved toward more naturalistic, ecologically valid paradigms. Here, I introduce this move in three frameworks: (i) sound stimulation and empirical paradigms, (ii) study participants, and (iii) methods and contexts of data acquisition. I wish to provide a narrative historical overview of the development of the field and, in parallel, to stimulate innovative thinking to further advance the ecological validity of the studies without overlooking experimental rigor.
Microbiome modulation after severe acute kidney injury accelerates functional recovery and decreases kidney fibrosis
Authors: Sepideh Gharaie, Kyungho Lee, Andrea M. Newman-Rivera, Jiaojiao Xu, Shishir Kumar Patel, Mahta Gooya, Lois J. Arend, Dominic S. Raj, Jennifer Pluznick, Chirag Parikh, Sanjeev Noel, Hamid Rabb
Journal: Kidney International (2023)
Early On-treatment Changes in Circulating Tumor DNA Fraction and Response to Enzalutamide or Abiraterone in Metastatic Castration-Resistant Prostate Cancer
Authors: Sofie H. Tolmeijer, Emmy Boerrigter, Takayuki Sumiyoshi, Edmond M. Kwan, Sarah W.S. Ng, Matti Annala, Gráinne Donnellan, Cameron Herberts, Guillemette E. Benoist, Paul Hamberg, Diederik M. Somford, Inge M. van Oort, Jack A. Schalken, Niven Mehra, Nielka P. van Erp, Alexander W. Wyatt
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Androgen receptor pathway inhibitors (ARPI) are standard of care for treatment-naïve metastatic castration-resistant prostate cancer (mCRPC), but rapid resistance is common. Early identification of resistance will improve management strategies. We investigated whether changes in circulating tumor DNA (ctDNA) fraction during ARPI treatment are linked with mCRPC clinical outcomes. Experimental Design: Plasma cell-free DNA was collected from 81 patients with mCRPC at baseline and after 4 weeks of first-line ARPI treatment during two prospective multicenter observational studies (NCT02426333; NCT02471469). ctDNA fraction was calculated from somatic mutations in targeted sequencing and genome copy-number profiles. Samples were classified into detected versus undetected ctDNA. Outcome measurements were progression-free survival (PFS) and overall survival (OS). Nondurable treatment response was defined as PFS ≤6 months. Results: ctDNA was detected in 48/81 (59%) baseline and 29/81 (36%) 4-week samples. ctDNA fraction for samples with detected ctDNA was lower at 4 weeks versus baseline (median 5.0% versus 14.5%, P = 0.017). PFS and OS were shortest for patients with persistent ctDNA at 4 weeks (univariate HR, 4.79; 95% CI, 2.62–8.77 and univariate HR, 5.49; 95% CI, 2.76–10.91, respectively), independent of clinical prognostic factors. For patients exhibiting change from detected to undetected ctDNA by 4 weeks, there was no significant PFS difference versus patients with baseline undetected ctDNA. ctDNA change had a positive predictive value of 88% and negative predictive value of 92% for identifying nondurable responses. Conclusions: Early changes in ctDNA fraction are strongly linked to duration of first-line ARPI treatment benefit and survival in mCRPC and may inform early therapy switches or treatment intensification. See related commentary by Sartor, p. 2745
Complexation of drug and hapten-conjugated aptamer with universal hapten antibody for pancreatic cancer treatment
Authors: Sun Il Choi, Yu-Sun Lee, Yul Min Lee, Hyun Jung Kim, Won Jong Kim, Sungjin Jung, Ji Eun Im, Mi Rim Lee, Joon Ki Kim, A-Ra Jeon, Sang Myung Woo, Goo Taeg Oh, Kyun Heo, Yun-Hee Kim, In-Hoo Kim
Journal: Journal of Controlled Release (2023)

Owing to a lack of reliable markers and therapeutic targets, pancreatic ductal adenocarcinoma (PDAC) remains the most lethal malignant tumor despite numerous therapeutic advances. In this study, we utilized cell-SELEX to isolate a DNA aptamer recognizing the natural conformation of the target on the cell surface. PAp7T8, an aptamer optimized by size and chemical modification, exhibited specific targeting to pancreatic cancer cells and orthotopic xenograft pancreatic tumors. To confer therapeutic functions to the aptamer, we adopted a drug-conjugated oligobody (DOligobody) strategy. Monomethyl auristatin E was used as a cytotoxic drug, digoxigenin acted as a hapten, and the humanized anti-digoxigenin antibody served as a universal carrier of the aptamer. The resulting PAp7T8-DOligobody showed extended in vivo half-life and markedly inhibited tumor growth in an orthotopic pancreatic cancer xenograft model without causing significant toxicity. Therefore, PAp7T8-DOligobody represents a promising novel therapeutic delivery platform for PDAC.
IFITM3 blocks influenza virus entry by sorting lipids and stabilizing hemifusion
Authors: Steffen Klein, Gonen Golani, Fabio Lolicato, Carmen Lahr, Daniel Beyer, Alexia Herrmann, Moritz Wachsmuth-Melm, Nina Reddmann, Romy Brecht, Mehdi Hosseinzadeh, Androniki Kolovou, Jana Makroczyova, Sarah Peterl, Martin Schorb, Yannick Schwab, Britta Brügger, Walter Nickel, Ulrich S. Schwarz, Petr Chlanda
Journal: Cell Host & Microbe (2023)
Mesenchymal Stem Cell Aggregation‐Released Extracellular Vesicles Induce CD31<sup>+</sup>EMCN<sup>+</sup> Vessels in Skin Regeneration and Improve Diabetic Wound Healing
Authors: Lu Liu, Chen‐Xi Zheng, Na Zhao, Ting Zhu, Cheng‐Biao Hu, Nan Zhang, Ji Chen, Kai‐Chao Zhang, Sha Zhang, Jie‐Xi Liu, Kai Zhang, Huan Jing, Bing‐Dong Sui, Yan Jin, Fang Jin
Journal: Advanced Healthcare Materials (2023)

The blood vessel system is essential for skin homeostasis and regeneration. While the heterogeneity of vascular endothelial cells has been emergingly revealed, whether a regeneration-relevant vessel subtype exists in skin remains unknown. Herein, a specialized vasculature in skin featured by simultaneous CD31 and EMCN expression contributing to the regeneration process is identified, the decline of which functionally underlies the impaired angiogenesis of diabetic nonhealing wounds. Moreover, enlightened by the developmental process that mesenchymal condensation induces angiogenesis, it is demonstrated that mesenchymal stem/stromal cell aggregates (CAs) provide an efficacious therapy to enhance regrowth of CD31+ EMCN+ vessels in diabetic wounds, which is surprisingly suppressed by pharmacological inhibition of extracellular vesicle (EV) release. It is further shown that CAs promote secretion of angiogenic protein-enriched EVs by proteomic analysis, which directly exert high efficacy in boosting CD31+ EMCN+ vessels and treating nonhealing diabetic wounds. These results add to the current knowledge on skin vasculature and help establish feasible strategies to benefit wound healing under diabetic condition.
Hepatocellular carcinomas, exhibiting intratumor fibrosis, express cancer-specific extracellular matrix remodeling and WNT/TGFB signatures, associated with poor outcome
Authors: Romain Desert, Wei Chen, Xiaodong Ge, Roselyne Viel, Hui Han, Dipti Athavale, Sukanta Das, Zhuolun Song, Daniel Lantvit, Luis Cano, Alexandra Naba, Orlando Musso, Natalia Nieto
Journal: Hepatology (2023)

Background and Aims: HCC, the third leading cause of cancer-related death, arises in the context of liver fibrosis. Although HCC is generally poorly fibrogenic, some tumors harbor focal intratumor extracellular matrix (ECM) deposits called “fibrous nests.” To date, the molecular composition and clinical relevance of these ECM deposits have not been fully defined. Approach and Results: We performed quantitative matrisome analysis by tandem mass tags mass spectrometry in 20 human cancer specific matrisome (HCCs) with high or low-grade intratumor fibrosis and matched nontumor tissues, as well as in 12 livers from mice treated with vehicle, carbon tetrachloride, or diethylnitrosamine. We found 94 ECM proteins differentially abundant between high and low-grade fibrous nests, including interstitial and basement membrane components, such as several collagens, glycoproteins, proteoglycans, enzymes involved in ECM stabilization and degradation, and growth factors. Pathway analysis revealed a metabolic switch in high-grade fibrosis, with enhanced glycolysis and decreased oxidative phosphorylation. Integrating the quantitative proteomics with transcriptomics from HCCs and nontumor livers (n = 2,285 samples), we identified a subgroup of fibrous nest HCCs, characterized by cancer-specific ECM remodeling, expression of the WNT/TGFB (S1) subclass signature, and poor patient outcome. Fibrous nest HCCs abundantly expressed an 11-fibrous-nest – protein signature, associated with poor patient outcome, by multivariate Cox analysis, and validated by multiplex immunohistochemistry. Conclusions: Matrisome analysis highlighted cancer-specific ECM deposits, typical of the WNT/TGFB HCC subclass, associated with poor patient outcomes. Hence, histologic reporting of intratumor fibrosis in HCC is of clinical relevance.
Vonoprazan-based versus proton pump inhibitor-based therapy in <i>Helicobacter pylori</i> eradication: an updated systematic review and meta-analysis of randomised trials
Authors: Po-Yueh Chen, Feng-Pai Tsai, Mei-Jyh Chen, Hsin-Yi Yang, Ming-Shiang Wu, Jyh-Ming Liou
Journal: Gut (2023)
Photoacoustic Imaging and Characterization of Bone in Medicine: Overview, Applications, and Outlook
Authors: Eduardo A. Gonzalez, Muyinatu A. Lediju Bell
Journal: Annual Review of Biomedical Engineering (2023)

Photoacoustic techniques have shown promise in identifying molecular changes in bone tissue and visualizing tissue microstructure. This capability represents significant advantages over gold standards (i.e., dual-energy X-ray absorptiometry) for bone evaluation without requiring ionizing radiation. Instead, photoacoustic imaging uses light to penetrate through bone, followed by acoustic pressure generation, resulting in highly sensitive optical absorption contrast in deep biological tissues. This review covers multiple bone-related photoacoustic imaging contributions to clinical applications, spanning bone cancer, joint pathologies, spinal disorders, osteoporosis, bone-related surgical guidance, consolidation monitoring, and transsphenoidal and transcranial imaging. We also present a summary of photoacoustic-based techniques for characterizing biomechanical properties of bone, including temperature, guided waves, spectral parameters, and spectroscopy. We conclude with a future outlook based on the current state of technological developments, recent achievements, and possible new directions.
Can adjuvant radiotherapy be omitted for oral cavity cancer patients who received neoadjuvant therapy and surgery? A retrospective cohort study
Authors: Wutong Ju, Yiyi Zhang, Ying Liu, Jingjing Sun, Jiang Li, Minjun Dong, Qi Sun, Wentao Shi, Tongchao Zhao, Zhihang Zhou, Yingying Huang, Xinyu Zhou, Dongwang Zhu, Shengjin Dou, Zhiyuan Zhang, Yue He, Chenping Zhang, Ronghui Xia, Guopei Zhu, Laiping Zhong
Journal: International Journal of Surgery (2023)

Surgery and postoperative adjuvant therapy comprise the standard treatment for locally advanced resectable oral squamous cell carcinoma (LAROSCC), while preoperative neoadjuvant therapy is being explored without sufficient confirmation of improved survival. De-escalation regimens after neoadjuvant therapy, such as those omitting adjuvant radiotherapy, may provide comparable or better outcomes, suggesting rigorous assessment of adjuvant therapy outcomes is needed in LAROSCC patients. The authors thus performed this retrospective study in LAROSCC patients who received neoadjuvant therapy and surgery, to compare the outcomes for overall survival (OS) and locoregional recurrence-free survival (LRFS) between the adjuvant radiotherapy (radio) and nonradiotherapy (nonradio) cohorts.Patients diagnosed with LAROSCC who received neoadjuvant therapy and surgery were enrolled and divided into radio and nonradio cohorts to determine whether adjuvant radiotherapy could be omitted after neoadjuvant therapy and surgery.From 2008 to 2021, 192 patients were enrolled. No significant differences were found in OS or LRFS between the radio and nonradio patient cohorts. The 10-year estimated OS rates were 58.9 versus 44.1% in radio versus nonradio cohorts, while 10-year estimated LRFS rates were 55.4 versus 48.2%, respectively. For clinical stage III patients, 10-year OS rates were 62.3 versus 62.6% (radio vs. nonradio), and estimated 10-year LRFS rates were 56.5 versus 60.7% (radio vs. nonradio). Multivariate Cox regression modeling of postoperative variables showed pathologic response of primary tumor and pathologic regional lymph nodes staging were associated with survival, while the adjuvant radiotherapy exposure was not included in the model due to nonsignificance.These findings support further prospective evaluation of adjuvant radiotherapy omission, and suggest that de-escalation trials are warranted for LAROSCC surgery patients who received neoadjuvant therapy.
Laparoscopic versus open repeat hepatectomy for recurrent hepatocellular carcinoma: a systematic review and meta-analysis of propensity score-matched cohort studies
Authors: Zhi-Qiang Xiang, Feng-Feng Zhu, Si-Qi Zhao, Hua-Jian Li, Zhang-Tao Long, Qian Wang, Xiao-Ming Dai, Zhu Zhu
Journal: International Journal of Surgery (2023)

Objective: The effectiveness of laparoscopic repeat hepatectomy (LRH) versus open repeat hepatectomy (ORH) on recurrent hepatocellular carcinoma (RHCC) is unclear. We compared the surgical and oncological outcomes of LRH and ORH in patients with RHCC with a meta-analysis of studies based on propensity score-matched cohorts. Methods: A literature search was conducted on PubMed, Embase, and Cochrane Library with Medical Subject Headings terms and keywords until 30 September 2022. The quality of eligible studies was evaluated with the Newcastle–Ottawa Scale. Mean difference (MD) with a 95% CI was used for the analysis of continuous variables; odds ratio (OR) with 95% CI was used for binary variables; and hazard ratio with 95% CI was used for survival analysis. A random-effects model was used for meta-analysis. Results: Five high-quality retrospective studies with 818 patients were included; 409 patients (50%) were treated with LRH and 409 (50%) with ORH. In most surgical outcomes, LRH was superior to ORH: less estimated blood loss, shorter operation time, lower major complication rate, and shorter length of hospital stay (MD=−225.9, 95% CI=[−360.8 to −91.06], P =0.001; MD=66.2, 95% CI=[5.28−127.1], P =0.03; OR=0.18, 95% CI=[0.05−0.57], P =0.004; MD=−6.22, 95% CI=[−9.78 to −2.67], P =0.0006). There were no significant differences in the remaining surgical outcomes: blood transfusion rate and overall complication rate. In oncological outcomes, LRH and ORH were not significantly different in 1-year, 3-year, and 5-year overall survival and disease-free survival. Conclusions: For patients with RHCC, most surgical outcomes with LRH were superior to those of ORH, but oncological outcomes with the two operations were similar. LRH may be a preferable option for the treatment of RHCC.
A3907, a systemic ASBT inhibitor, improves cholestasis in mice by multiorgan activity and shows translational relevance to humans
Authors: Francisco J. Caballero-Camino, Pedro M. Rodrigues, Fredrik Wångsell, Aloña Agirre-Lizaso, Paula Olaizola, Laura Izquierdo-Sanchez, Maria J. Perugorria, Luis Bujanda, Bo Angelin, Sara Straniero, Anna Wallebäck, Ingemar Starke, Per-Göran Gillberg, Ellen Strängberg, Britta Bonn, Jan P. Mattsson, Martin R. Madsen, Henrik H. Hansen, Erik Lindström, Peter Åkerblad, Jesus M. Banales
Journal: Hepatology (2023)

Cholestasis is characterized by intrahepatic accumulation of bile constituents, including bile acids (BAs), which promote liver damage. The apical sodium-dependent BA transporter (ASBT) plays an important role in BA reabsorption and signaling in ileum, bile ducts, and kidneys. Our aim was to investigate the pharmacokinetics and pharmacological activity of A3907, an oral and systemically available ASBT inhibitor in experimental mouse models of cholestasis. In addition, the tolerability, pharmacokinetics, and pharmacodynamics of A3907 were examined in healthy humans.